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Structural Covariance of Cortical Gyrification at Illness Onset in Treatment Resistance: A Longitudinal Study of First-Episode Psychoses

Ajnakina, O; Das, T; Lally, J; Di Forti, M; Pariante, CM; Marques, TR; Mondelli, V; ... Dazzan, P; + view all (2021) Structural Covariance of Cortical Gyrification at Illness Onset in Treatment Resistance: A Longitudinal Study of First-Episode Psychoses. Schizophrenia Bulletin 10.1093/schbul/sbab035. (In press).

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Abstract

Treatment resistance (TR) in patients with first-episode psychosis (FEP) is a major cause of disability and functional impairment, yet mechanisms underlying this severe disorder are poorly understood. As one view is that TR has neurodevelopmental roots, we investigated whether its emergence relates to disruptions in synchronized cortical maturation quantified using gyrification-based connectomes. Seventy patients with FEP evaluated at their first presentation to psychiatric services were followed up using clinical records for 4 years; of these, 17 (24.3%) met the definition of TR and 53 (75.7%) remained non-TR at 4 years. Structural MRI images were obtained within 5 weeks from first exposure to antipsychotics. Local gyrification indices were computed for 148 contiguous cortical regions using FreeSurfer; each subject's contribution to group-based structural covariance was quantified using a jack-knife procedure, providing a single deviation matrix for each subject. The latter was used to derive topological properties that were compared between TR and non-TR patients using a Functional Data Analysis approach. Compared to the non-TR patients, TR patients showed a significant reduction in small-worldness (Hedges's g = 2.09, P < .001) and a reduced clustering coefficient (Hedges's g = 1.07, P < .001) with increased length (Hedges's g = -2.17, P < .001), indicating a disruption in the organizing principles of cortical folding. The positive symptom burden was higher in patients with more pronounced small-worldness (r = .41, P = .001) across the entire sample. The trajectory of synchronized cortical development inferred from baseline MRI-based structural covariance highlights the possibility of identifying patients at high-risk of TR prospectively, based on individualized gyrification-based connectomes.

Type: Article
Title: Structural Covariance of Cortical Gyrification at Illness Onset in Treatment Resistance: A Longitudinal Study of First-Episode Psychoses
Location: United States
DOI: 10.1093/schbul/sbab035
Publisher version: http://dx.doi.org/10.1093/schbul/sbab035
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: MRI, clozapine, first-episode psychosis, gyrification, longitudinal, schizophrenia, treatment-resistant
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Behavioural Science and Health
URI: https://discovery.ucl.ac.uk/id/eprint/10126495
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